Biomarkers for use in prognosis of mortality in critically ill patients

Abstract

Biomarkers and methods of using them for aiding diagnosis, prognosis, and treatment of critically ill patients are disclosed. In particular, the invention relates to the use of biomarkers for prognosis of mortality in critically ill patients with sepsis, severe trauma, or burns.

What is claimed is: 
     
       1. A method administering urgent care to a patient, comprising:
 a) obtaining a biological sample from the patient; 
 b) detecting levels of expression of DEFA4, CD163, PER1, RGS1, HIF1A, SEPP1, C11orf74, CIT, LY86, TST, and KCNJ2 biomarkers in the biological sample; 
 c) identifying the patient as having a high risk of mortality within 30 days, wherein the patient has increased levels of expression of the DEFA4, CD163, PER1, RGS1, HIF1A, SEPP1, C11orf74, and CIT biomarkers and decreased levels of expression of the LY86, TST, and KCNJ2 biomarkers compared to reference value ranges; and 
 d) administering an antimicrobial therapy to the patient, administering an immune-modulating therapy to the patient, or administering an organ-specific treatment to the patient. 
 
     
     
       2. The method of  claim 1 , wherein detecting the levels of expression of the biomarkers comprises performing microarray analysis, polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT-PCR), a Northern blot, a serial analysis of gene expression (SAGE), or isothermal amplification. 
     
     
       3. The method of  claim 1 , wherein the biological sample comprises blood, buffy coat, band cells, or metamyelocytes. 
     
     
       4. The method of  claim 1 , wherein the levels of the biomarkers are compared to time-matched reference values for infected or non-infected subjects. 
     
     
       5. The method of  claim 1 , wherein the organ-specific treatment comprises either or both of connecting the patient to any one or more of a mechanical ventilator, a pacemaker, a defibrillator, a dialysis or renal replacement therapy machine, an invasive monitor including a pulmonary artery catheter, arterial blood pressure catheter, or central venous pressure catheter, or administering blood products, vasopressors, or sedatives. 
     
     
       6. A kit comprising agents for detecting the levels of expression of up to 30 biomarkers, wherein the up to 30 biomarkers comprise DEFA4, CD163, PER1, RGS1, HIF1A, SEPP1, C11orf74, CIT, LY86, TST, and KCNJ2 transcripts. 
     
     
       7. The kit of  claim 6 , wherein the kit comprises a microarray. 
     
     
       8. The kit of  claim 7 , further comprising information, in electronic or paper form, comprising instructions to correlate the detected levels of the biomarkers with mortality risk. 
     
     
       9. The kit of 50, wherein the kit comprises: an oligonucleotide that hybridizes to a DEFA4 polynucleotide, an oligonucleotide that hybridizes to a CD163 polynucleotide, an oligonucleotide that hybridizes to a PER1 polynucleotide, an oligonucleotide that hybridizes to a RGS1 polynucleotide, an oligonucleotide that hybridizes to an HIF1A polynucleotide, an oligonucleotide that hybridizes to a SEPP1 polynucleotide, an oligonucleotide that hybridizes to a C11orf74 polynucleotide, an oligonucleotide that hybridizes to a CIT polynucleotide, an oligonucleotide that hybridizes to a LY86 polynucleotide, an oligonucleotide that hybridizes to a TST polynucleotide, and an oligonucleotide that hybridizes to a KCNJ2 polynucleotide.